title: Local kallikrein-kinin system is involved in podocyte apoptosis under diabetic conditions.
abstract: The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10(-7) mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10(-8) mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
authors.affiliation: Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Shinchon-Dong, Seodaemoon-Gu, Seoul, Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Kwak
authors.forename: Jisun
authors.initials: J
authors.lastname: Paeng
authors.forename: Do Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Lee
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Nam
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kang
authors.forename: Jin Ji
authors.initials: JJ
authors.lastname: Li
authors.forename: Dong-Sub
authors.initials: DS
authors.lastname: Jung
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Han
authors.forename: Dong-Ryeol
authors.initials: DR
authors.lastname: Ryu
authors.forename: Jung Tak
authors.initials: JT
authors.lastname: Park
authors.forename: Tae Ik
authors.initials: TI
authors.lastname: Chang
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Yoo
authors.forename: Dae Suk
authors.initials: DS
authors.lastname: Han
authors.forename: Shin-Wook
authors.initials: SW
authors.lastname: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D016234:Kallikrein-Kinin System; D008297:Male; D051379:Mice; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005947:Glucose; D001920:Bradykinin